Contemporary therapy for patients with HF associated with systolic dysfunction includes an imposing range of drugs (angiotensin-converting enzyme inhibitors, β-blockers, aldosterone antagonists, diuretics, angiotensin receptor blockers, nitrates/hydralazine, and digoxin) and devices (biventricular pacemakers and implantable cardioverter defibrillators). The inclusion of these therapies in international guidelines1 has been the product of decades of clinical research focusing on outcomes, specifically reducing HF-associated hospitalizations and mortality. Although efforts to develop new therapies have frequently incorporated quality-of-life and functional measures, they are rarely the primary goal of a development program. The emergence of nonpharmacologic approaches that attempt to directly improve quality of life, such as mind-body medicine,2 poses new challenges in the evaluation of efficacy in HF trials. Should the clinical trialist, and eventually the clinician, select primary study end points that emphasize objective increases in functional activity? Or should improvements in the patient's subjective sense of well-being be the focus?